Oxaliplatin, Fludarabine, and Cytarabine in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)

NCT ID: NCT00480987

Last Updated: 2012-08-07

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2010-08-31

Brief Summary

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The goal of this clinical research study is to find the highest tolerable dose of oxaliplatin combined with fludarabine plus cytarabine that can be given to patients with Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS). Once the highest tolerable dose of oxaliplatin in this drug combination is found, the next goal of the study will be to learn the safety and the ability of the drug combination to control the disease.

Detailed Description

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The Study Drugs:

Cytarabine is designed to insert itself into Deoxyribonucleic acid (DNA) (the genetic material of cells) and stop the DNA from repairing itself.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Oxaliplatin is designed to "program" cells to cause death in leukemic cells.

The Phases of The Study:

This research study has 2 parts, Phase I and Phase II.

The Phase I part of the study will be used to test different dose levels in order to determine the highest tolerable dose of the study drug oxaliplatin that can be given in combination with cytarabine and fludarabine to patients with AML or high-risk MDS. Three (3) participants will be enrolled at each dose level until the highest tolerable dose is found.

The Phase II part of the study will evaluate the safety and disease-control ability of the study drug combination (the highest tolerable dose that was found) in order to treat these patients.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be given oxaliplatin through a needle (intravenously -- through an IV) in your vein over 2 hours for 4 days (Days 1-4) in a row.

On Day 2, you will be given cytarabine through an IV in your vein by continuous infusion over 24 hours for 5 days (Days 2-6) in a row. Starting on Day 2, you will be given fludarabine through an IV in your vein over 30 minutes for 5 days (Days 2-6) in a row. In order to keep you from being dehydrated, you will also be given other IV fluids, such as saline (a salt solution), each day you receive the study drugs. If the drugs are given on an outpatient basis, a daily visit may take about 8 hours.

One (1) cycle is 6 days long. The first cycle will be given at M. D. Anderson. Each cycle will be repeated every 4-6 weeks. Depending on your response to the study drug combination, you will have up to 5 more cycles either at M. D. Anderson or on an outpatient basis with your regular physician.

Your study drug dose may be lowered if you experience severe side effects.

Study Visits:

During each treatment cycle, you will have blood drawn (about 1 teaspoon each time) at least 2-3 times a week for routine tests. You will have a bone marrow aspiration done on Day 21 of Cycle 1 and once a week thereafter, unless there is clear evidence of active disease. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You will remain on this study for up to 6 cycles for a total of about 6 months, unless the disease is not responding, the disease gets worse, or you experience intolerable side effects. If you are taken off this study early, your study doctor will discuss other treatment options with you.

End-of-Treatment Visit:

Once you have completed treatment on this study, you will have an end-of-treatment visit. This visit will include routine blood tests (about 1 teaspoon will be drawn each time) and a bone marrow aspirate to check the status of the disease. If your blood tests show the disease has gotten worse, no bone marrow aspirate will be needed.

Long-Term Follow-up:

After your last cycle of treatment is completed and every 3 months for as long as you are in remission, you will have blood drawn (about 2 teaspoons each) for routine testing.

This is an investigational study. Cytarabine is Food and Drug Administration (FDA) approved and commercially available for the treatment of AML and other blood cancers. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Oxaliplatin is FDA approved and commercially available for the treatment of advanced colorectal cancer and colon cancer. Their use in combination is investigational in this study.

Conditions

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Myelodysplastic Syndromes Acute Myeloid Leukemia Leukemia

Keywords

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High-Risk Myelodysplastic Syndromes Acute Myeloid Leukemia Leukemia Oxaliplatin Fludarabine Cytarabine AML MDS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oxaliplatin + Cytarabine + Fludarabine

Oxaliplatin 30 mg/m\^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m\^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m\^2 IV days 2-6

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

30 mg/m\^2 IV days 1-4

Fludarabine

Intervention Type DRUG

30 mg/m\^2 IV days 2-6

Cytarabine

Intervention Type DRUG

500 mg/m\^2 by IV continuous infusion days 2-6

Interventions

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Oxaliplatin

30 mg/m\^2 IV days 1-4

Intervention Type DRUG

Fludarabine

30 mg/m\^2 IV days 2-6

Intervention Type DRUG

Cytarabine

500 mg/m\^2 by IV continuous infusion days 2-6

Intervention Type DRUG

Other Intervention Names

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Eloxatin® Fludara® Fludarabine Phosphate Ara-C

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome.
* Performance status 0-2 (Zubrod scale).
* Serum creatinine equal or less than 1.3 mg/dL or creatinine clearance \> 40 mL/min.
* Bilirubin \</= 2 mg/dL; serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) \</= 3 times the Upper Limit of Normal (ULN) for the reference lab unless due to leukemia or congenital hemolytic disorder (for bilirubin).
* Written informed consent.

Exclusion Criteria

* No untreated or uncontrolled life-threatening infection.
* No oxaliplatin, fludarabine, or cytarabine intolerance.
* No pregnancy or lactation. Female patients of childbearing potential (including those \< 1 year post-menopausal) and male patients must agree to use contraception.
* No chemotherapy or radiation therapy within 4 weeks of study entry. Hydroxyurea is allowed prior to starting therapy in the setting of rapidly proliferating disease.
* No other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent or cooperate and participate in the study or to interfere with the interpretation of the results.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gautam Borthakur, M.D.

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://mdanderson.org

UT MD Anderson Cancer Center website

Other Identifiers

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2006-1089

Identifier Type: -

Identifier Source: org_study_id